The Massachusetts (MA) Center for Birth Defects Research and Prevention (MCBDRP) proposes to continue its strong track record of conducting etiologic research to identify modifiable risk factors for structural birth defects through its participation in the Birth Defects Study to Evaluate Pregnancy exposureS II (BD-STEPS II). We will enhance our contributions by leveraging our longstanding relationship with local universities to produce future birth defects researchers. The MCBDRP brings to BD-STEPS II our expertise and leadership in pharmacoepidemiology and collaborative utilization of unique data resources to be applied to all three key areas of interest named in the Notice of Funding Opportunity. Our research will utilize existing data from the National Birth Defects Prevention Study, BD-STEPS I and data to be collected as part of BD-STEPS II. The MCBDRP investigators are committed and successful mentors and collaborative partners, roles that will continue and expand within BD-STEPS II. Over the five year grant period, the MCBDRP will complete at least 10 etiologic research projects of public health significance that will aid in counseling women in considering exposures that are less likely to result in a birth defect; these projects include: 1) Evaluating nicotinamide adenine dinucleotide pathway inhibitors and the potential preventive effect of supplementation with niacin; 2) Examining anti-viral medications, which are key to preventing maternal-fetal transmission but little is known on their safety with respect to birth defects; 3) Assessing anti-obesity medications that have been and will continue to be approved by FDA and assessing bariatric surgical procedures that are increasingly performed; 4) Investigating attention deficit hyperactivity disorder medications, the use of which has increased dramatically; 5) Gauging the complex relationship among multiple risk factors to further our understanding of birth defects; 6) Exploring trends in medication use in pregnancy to identify drugs that are becoming relatively commonly used in pregnancy; 7) Leveraging the State Lab's reportable disease database to explore the role of infections before and during pregnancy on the development of birth defects; 8) Considering folate pathway co- factors, that support the one-carbon metabolism pathway, and their role in neural tube development; 9) Exploring limb reduction deficiencies that are accompanied by amniotic bands and terminal transverse limb defects to understand if they share common risk factors and pathogenesis; and 10) Harnessing this unique data source to assess the relative risks/safety in pregnancy of newly-introduced medications, which is essential given there is no ongoing, systematic approach to monitor drug safety in pregnancy in the US. For our medication validation pilot study we will consider prescription drugs derived from the initial prescription (medical record), pharmacy dispensing (claims data) and maternal report of use (prospectively collected data in a mobile application). Through these activities, the MCBDRP will be an essential partner in BD-STEPS II to achieve our overall goal of translating research findings into meaningful initiatives in birth defects prevention.